Reus injured ankle ligaments for the third time in five months in Dortmund's 1-0 win over Borussia Monchengladbach before the international break, a blow that forced him to miss Germany's Euro 2016 qualifier with Gibraltar and the friendly against Spain.
However, the 25-year-old is now back to fitness and will be available for selection as Dortmund look to build on the Monchengladbach victory following a dreadful start to the season.
Striker Pierre-Emerick Aubameyang has returned to training following muscular problems, while full-back Lukasz Piszczek is expected to play despite a back issue.
Nuri Sahin, Jakub Blaszczykowski and Oliver Kirch, all of whom have suffered from injury troubles, are in contention to feature at some point but defenders Mats Hummels (foot) and Sokratis Papastathopoulos (leg) are out.
"Marco Reus is fit to play against SC Paderborn," Klopp said on Thursday. "Sahin, Blaszczykowski and Kirch are not as far as Reus, ideally we still are able to give them some time.
"Aubameyang had muscular problems and then gastric flu, but he'll return to training today. Piszczek should be fit to play against Paderborn.
"Hummels is not as far as we have planned, hopefully he'll be an option for Wednesday [in the UEFA Champions League game with Arsenal]. Sokratis is still limping a bit, so I hope Hummels is available on Wednesday."
Paderborn have enjoyed a decent start to their first season in the German top flight and sit in ninth position, five points ahead of struggling Dortmund.
And Klopp is wary of the quality of Andre Breitenreiter's men.
"I have the maximum respect for all that is happening at SC Paderborn right now," he added.
"Paderborn is an example that you can achieve something in football with not a lot of money, a good idea and many right decisions.
"There is hardly anything Paderborn can't do."